Effects of TLR-2/NF-κB signaling pathway on the occurrence of degenerative knee osteoarthritis: an in vivo and in vitro study

Abstract

The study aims to explore the effects of TLR-2/NF-κB signaling pathway on the occurrence of degenerative knee osteoarthritis (OA). Degenerative knee OA and normal cartilage samples were collected from patients with degenerative knee OA receiving total knee arthroplasty and amputation. Expressions of TLR-2, NF-κB and MMP-13 were determined by qRT-PCR and immunochemistry. The chondrocytes were divided into control, IL-1β, IL-1β + anti-TLR-2 and IL-1β + PDTC groups. MTT assay and flow cytometry were performed to determine proliferation and apoptosis of the chondrocytes. Expressions of TLR-2, NF-κB and MMP-13 were measured by Western blotting. ELISA was conducted to detect the expressions of related inflammatory factors. The positive expressions of TLR, NF-κB and MMP13 were associated with body mass index (BMI), family history, exercise, and WOMAC scores of OA patients. Logistic regression analysis showed that OA influencing factors were TLR, NF-κB, MMP13, BMI, family history and exercise. Compared with normal chondrocytes, the expressions of TLR-2, NF-κB, MMP-13 and related inflammatory factors increased in degenerative knee OA. The chondrocytes in the IL-1β + anti-TLR-2 and IL-1β + PDTC groups showed lower apoptosis rates than those in the IL-1β group. Compared with the control group, increased expressions of TLR-2, NF-κB, phosphorylated-NF-κB (p-NF-κB), MMP-13, IL-1, IL-6 and TNF-α were found in the IL-1β group. In the IL-1β + anti-TLR-2 and IL-1β + PDTC groups, decreased expressions of NF-κB, p-NF-κB, MMP-13, IL-1, IL-6 and TNF-α were found compared with those in the IL-1β group. TLR-2/NF-κB signaling pathway contributes to the occurrence of degenerative knee OA.

Differential miRNAomics of the synovial membrane in knee osteoarthritis induced by bilateral anterior cruciate ligament transection in rats

“…The causes of pathological alterations in synovitis include the release of proinflammatory cytokines and oxidative stress damage. Although a number of inflammatory factors, including tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-18 and NACHT, LRR and PYD domains-containing protein 3 (NLRP3), are involved in the process of synovitis, there are few reports of small molecules that progressively degenerate articular synovial membrane in KOA (4,5).…”

Estrogen reverses nicotine‐induced inflammation in chondrocytes via reducing the degradation of ECM

“…In chondrocytes, the most representative metalloproteases that degrade collagen and proteoglycans are MMP13 (matrix metalloproteinases 13) and ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs 5), respectively . The expression of these enzymes can be regulated by inflammatory factors and growth factors, such as TNF‐α, IL‐1β, TGF‐β and so on …”

Expression profiling of LncRNA and miRNA in SDF-1-induced articular chondrocyte degeneration

“…During infection, TLR signaling is necessary for the proper activation of the body's immune response (22) TLRs produce a large amount of IL-1β and TNF-α in ammatory factors by activating the NK-κB in ammatory signaling pathway. Liu et al (23) found that the expression of TLR-2, NF-κB, MMP-13 and related in ammatory factors were signi cantly up-regulated with the severity of OA lesions, suggesting that TLR-2 / NF-κB signaling pathway may be involved in the occurrence of OA.…”